The majority of clinical methods used to assess the severity of aortic regurgitation are based on an assessment of regurgitant volume or left ventricular chamber dimensions. While these methods have improved the evaluation of patients with aortic regurgitation, the natural history of the disorder remains incompletely defined due to the lack of understanding of the role of the regurgitant orifice area. The long-term objective of this proposal is to develop an understanding of the regurgitant orifice area, aortic root dynamics, and retrograde aortic flow profiles in the normal state and in aortic regurgitation. The applicant has developed methods of estimating the regurgitant orifice area in aortic regurgitation and has demonstrated that the regurgitant orifice area is pressure-dependent in an animal model of acute aortic regurgitation. To evaluate the importance and nature of the regurgitant orifice area in aortic regurgitation, this proposal aims: 1) to test the hypothesis that the regurgitant orifice area is dependent on aortic root geometry using an in vitro flow system, 2) to describe the retrograde aortic flow profile and determine the regurgitant volume and orifice area in acute aortic regurgitation using magnetic resonance velocity mapping and echocardiography, 3) to test the hypothesis that the regurgitant orifice area in patients with chronic aortic regurgitation is load-dependent using invasive catheterization techniques, and 4) to establish the relationship between new invasive and noninvasive Doppler parameters of regurgitant severity. The major long-term objective for the applicant is to apply the basic principles of fluid mechanics to the cardiovascular system. Achieving this goal will be possible by completing courses in basic and cardiovascular fluid mechanics at Massachusetts Institute of Technology. 'Re applicant will become independent in using these principles to investigate a variety of problems in cardiovascular physiology and develop her career. The ultimate goal is to develop new quantitative indices of aortic regurgitation severity that will improve the management of patients with aortic regurgitant and enhance the understanding of the underlying disorder.